Data from MicroRNA-202-3p Inhibits Cell Proliferation by Targeting ADP-Ribosylation Factor-like 5A in Human Colorectal Carcinoma

Abstract

<div>Abstract<p><b>Purpose:</b> MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of non–protein-coding RNAs. Here, we focused on the function and molecular mechanism of <i>miR-202-3p</i> and its potential clinical application in colorectal cancer.</p><p><b>Experimental Design:</b><i>miR-202-3p</i> expression was determined by quantitative reverse transcriptase PCR (qRT-PCR) in 94 colorectal cancer tissues and corresponding noncancerous tissues (NCT). Cell proliferation and colony formation assays <i>in vitro</i> and xenograft experiments <i>in vivo</i> were used to evaluate the effect of <i>miR-202-3p</i> on colorectal cancer cell proliferation. Luciferase assay and Western blot analysis were performed to validate the potential targets of <i>miR-202-3p</i> after the preliminary screening by online prediction and microarray analysis. The mRNA and protein levels of target genes were detected by qRT-PCR and immunohistochemical staining. The copy number of <i>pre-miR-202</i> was measured by quantitative PCR.</p><p><b>Results:</b> First, <i>miR-202-3p</i> was significantly downregulated in 46.7% colorectal cancer samples compared with NCTs. The overexpression of <i>miR-202-3p</i> inhibited colorectal cancer cell growth <i>in vitro</i> and repressed tumorigenesis in nude mice. Then, <i>miR-202-3p</i> downregulated ADP-ribosylation factor-like 5A (<i>ARL5A</i>) protein level by binding to its 3′ untranslated region, and knockdown of <i>ARL5A</i> phenocopied the proliferation inhibition effect of <i>miR-202-3p</i>. Furthermore, both of <i>ARL5A</i> mRNA and protein levels were upregulated in colorectal cancer samples compared with NCTs and high <i>ARL5A</i> protein levels predicted a poor prognosis.</p><p><b>Conclusions:</b><i>miR-202-3p</i> might function as a tumor suppressor in colorectal cancer, and <i>ARL5A</i>, the functional target of <i>miR-202-3p</i> in colorectal cancer, is a potential prognostic factor for colorectal cancer. <i>Clin Cancer Res; 20(5); 1146–57. ©2013 AACR</i>.</p></div>